Cláudia Alves Couto

Antismooth Muscle and Antiactin Antibodies Are Indirect Markers of Histological and Biochemical Activity of Autoimmune Hepatitis

Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4‐69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2‐6] times) after a mean follow‐up evaluation of 70 [20‐185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti‐LKM1), antiliver cytosol type 1 (anti‐LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow‐up evaluation through indirect immunofluorescence in rodent tissues, HEp‐2 cells, and human fibroblasts. Anti‐SLA/LP were assessed 45 times in the follow‐up evaluation of 19 patients using enzyme‐linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti‐SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). Conclusion: With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. (Hepatology 2014;59:592–600)

The role of intestinal bacteria overgrowth in obesity-related nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It is a progressive disorder involving a spectrum of conditions that include pure steatosis without inflammation, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes, which may be followed by lipid peroxidation, production of reactive oxygen species and consequent inflammation. Recent studies suggest that the characteristics of the gut microbiota are altered in NAFLD, and also, that small intestinal bacterial overgrowth (SIBO) contributes to the pathogenesis of this condition. This review presents the chief findings from all the controlled studies that evaluated SIBO, gut permeability and endotoxemia in human NAFLD. We also discuss the possible mechanisms involving SIBO, lipid accumulation and development of NASH. The understanding of these mechanisms may allow the development of new targets for NASH treatment in the future.

Portal Vein Thrombosis and Budd–Chiari Syndrome

Venous thrombosis results from the convergence of vessel wall injury and/or venous stasis, known as local triggering factors, and the occurrence of acquired and/or inherited thrombophilia, also known as systemic prothrombotic risk factors. Portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS) are caused by thrombosis and/or obstruction of the extrahepatic portal veins and the hepatic venous outflow tract, respectively. Several divergent prothrombotic disorders may underlie these distinct forms of large vessel thrombosis. While cirrhotic PVT is relatively common, especially in advanced liver disease, noncirrhotic and nontumoral PVT is rare and BCS is of intermediate incidence. In this article, we review pathogenic mechanisms and current concepts of patient management.

Probiotics as a complementary therapeutic approach in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditions that include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.

Dietary patterns in Brazilian patients with nonalcoholic fatty liver disease: a cross-sectional study.

OBJECTIVE: Recent evidence suggests that non-alcoholic fatty liver disease is associated with diet. Our aim was to investigate the dietary patterns of a Brazilian population with this condition and compare them with the recommended diet. METHODS: A cross-sectional study was conducted on 96 non-alcoholic fatty liver disease patients before any dietetic counseling. All patients underwent abdominal ultrasound, biochemical tests, dietary evaluations, and anthropometric evaluations. Their food intake was assessed by a semi-quantitative food-frequency questionnaire and 24-hour food recall. RESULTS: The median patient age was 53 years, and 77% of the individuals were women. Most (67.7%) participants were obese, and a large waist circumference was observed in 80.2% subjects. Almost 70% of the participants had metabolic syndrome, and 62.3% presented evidence of either insulin resistance or overt diabetes. Most patients (51.5, 58.5, and 61.7%, respectively) exceeded the recommendations for energy intake, as well as total and saturated fat. All patients consumed less than the amount of recommended monounsaturated fatty acids, and 52.1 and 76.6% of them consumed less polyunsaturated fatty acids and fiber, respectively, than recommended. In most patients, the calcium, sodium, potassium, pyridoxine, and vitamin C intake did not meet the recommendations, and in 10.5-15.5% of individuals, the tolerable upper limit intake for sodium was exceeded. The patients presented a significantly high intake of meats, fats, sugars, legumes (beans), and vegetables and a low consumption of cereals, fruits, and dairy products compared with the recommendations. CONCLUSIONS: Although patients with non-alcoholic fatty liver disease exhibited high energy and lipid consumption, most of them had inadequate intake of some micronutrients. The possible role of nutrient-deficient intake in the development of non-alcoholic fatty liver disease warrants investigation.

Dietary approach in the treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has been identified as one of the most prevalent chronic liver disease in adults and children populations. NAFLD is usually associated with the metabolic syndrome (MS), which is chiefly related to insulin resistance and its consequences. Insulin resistance has a crucial role in the pathogenesis of hepatic steatosis and potentially nonalcoholic steatohepatitis (NASH). Because of the contemporary epidemics of MS and obesity, the burden of NAFLD is also expected to rise. Unhealthy diets, such as the so-called western diet, are enriched in fructose, trans-fatty acids and saturated fat and seem to be associated with the development of NAFLD. In human studies, certain dietary sugars, particularly fructose, are used as a substrate for lipogenesis leading to hepatic fatty infiltration, inflammation, and possibly fibrosis. Other investigations have shown that fat consumption especially cholesterol and trans/saturated fatty acids are also steatogenic and seem to increase visceral adiposity. The identification of specific dietary components that favor the development of NASH could be important for the management of this disorder. This review focuses on the effects of different dietary approaches to prevent and treat NAFLD emphasizing the macronutrients and energy composition.

Recurrent and de novo autoimmune liver diseases.

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) each account for approximately 5% of liver transplants per year performed in the United States and Europe. Even though outcomes are excellent, with reported 5-year patient and graft survival exceeding 90% and 80%, 80% and 75%, 72% and 65% for PBC, PSC, and AIH, respectively, the issue of recurrent autoimmune liver disease after orthotopic liver transplantation is increasingly recognized as a cause of graft dysfunction, death, and need for retransplantation. This article reviews diagnostic criteria, epidemiology, risk factors, and outcomes of recurrent PBC, PSC, and AIH after liver transplantation.

Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries; it can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocarcinoma. The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients. In a randomized, controlled clinical trial, involving 50 biopsy-proven NASH patients, we investigated the effects of synbiotic supplementation on metabolic parameters, hepatic steatosis, intestinal permeability, small intestinal bacterial overgrowth (SIBO) and lipopolysaccharide (LPS) serum levels. Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone. Before and after the intervention we assessed steatosis by magnetic resonance imaging, intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing. NASH patients presented high gut permeability, but low prevalence of SIBO. After the intervention, only the synbiotic group presented a reduction in steatosis, lost weight, diminished BMI and waist circumference measurement. Synbiotic did not improve intestinal permeability or LPS levels. We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss.

A Novel Wistar Rat Model of Obesity-Related Nonalcoholic Fatty Liver Disease Induced by Sucrose-Rich Diet

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is not fully understood, and experimental models are an alternative to study this issue. We investigated the effects of a simple carbohydrate-rich diet on the development of obesity-related NAFLD and the impact of physical training on the metabolic abnormalities associated with this disorder. Sixty Wistar rats were randomly separated into experimental and control groups, which were fed with sucrose-enriched (18% simple carbohydrates) and standard diet, respectively. At the end of each experimental period (5, 10, 20, and 30 weeks), 6 animals from each group were sacrificed for blood tests and liver histology and immunohistochemistry. From weeks 25 to 30, 6 animals from each group underwent physical training. The experimental group animals developed obesity and NAFLD, characterized histopathologically by steatosis and hepatocellular ballooning, clinically by increased thoracic circumference and body mass index associated with hyperleptinemia, and metabolically by hyperglycemia, hyperinsulinemia, hypertriglyceridemia, increased levels of very low-density lipoprotein- (VLDL-) cholesterol, depletion of the antioxidants liver enzymes superoxide dismutase and catalase, and increased hepatic levels of malondialdehyde, an oxidative stress marker. Rats that underwent physical training showed increased high-density lipoprotein- (HDL-) cholesterol levels. In conclusion, a sucrose-rich diet induced obesity, insulin resistance, oxidative stress, and NAFLD in rats.

SEVERE AND PROLONGED CHOLESTASIS CAUSED BY TRIMETHOPRIM-SULFAMETHOXAZOLE: A CASE REPORT

Trimethoprim-sulfamethoxazole (TMP-SMX) is a widely used antibiotic in the prophylaxis and treatment of a variety of common infections. Hepatic injuries caused by TMP-SMX are considered rare and are classified as unpredictable or idiosyncratic types of hepatotoxic reactions.1 The pattern of injury may be characterized by hepatocellular necrosis,1,2 mixed hepatocellular-cholestasis,1,3,4 or cholestasis.5–7 We describe a case of severe and prolonged cholestasis, which arose 30 days after a 5-day course of TMP-SMX treatment, and provide a review of related cases.